Current Treatment of Oral Candidiasis: A Literature Review

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J Clin Exp Dent. 2014;6(5):e576-82.

Treatment of oral candidiasis

Journal section: Oral Medicine and Pathology doi:10.4317/jced.51798


Publication Types: Review http://dx.doi.org/10.4317/jced.51798

Current treatment of oral candidiasis: A literature review

Carla Garcia-Cuesta 1, Maria-Gracia Sarrion-Pérez 2, Jose V. Bagán 3

1
Dentist. Postgraduate in Oral Medicine
2
Associate profesor of Oral Medicine Unit. Department of Stomatology. University of Valencia
3
Chairman of Oral Medicine. Oral Medicine Unit. Department of Stomatology. University of Valencia. Head of the Department of
Stomatology and Maxilofacial Surgery. Valencia University General Hospital

Correspondence:
Avd. / Maestro Rodrigo 13-16 Garcia-Cuesta C, Sarrion-Pérez MG, Bagán JV. Current treatment of oral
46015 Valencia, Spain candidiasis: A literature review. J Clin Exp Dent. 2014;6(5):e576-82.
carlagcuesta@gmail.com http://www.medicinaoral.com/odo/volumenes/v6i5/jcedv6i5p576.pdf

Article Number: 51798 http://www.medicinaoral.com/odo/indice.htm


© Medicina Oral S. L. C.I.F. B 96689336 - eISSN: 1989-5488
Received: 19/06/2014 eMail: jced@jced.es
Accepted: 26/07/2014 Indexed in:
Pubmed
Pubmed Central® (PMC)
Scopus
DOI® System

Abstract
Candidiasis or oral candidosis is one of the most common human opportunistic fungal infections of the oral cavity.
This pathology has a wide variety of treatment which has been studied until these days. The present study offers
a literature review on the treatment of oral candidiasis, with the purpose of establish which treatment is the most
suitable in each case. Searching the 24 latest articles about treatment of candidiasis it concluded that the incidence
depends on the type of the candidiasis and the virulence of the infection. Although nystatin and amphotericin b were
the most drugs used locally, fluconazole oral suspension is proving to be a very effective drug in the treatment of
oral candidiasis. Fluconazole was found to be the drug of choice as a systemic treatment of oral candidiasis. Due
to its good antifungal properties, its high acceptance of the patient and its efficacy compared with other antifungal
drugs. But this drug is not always effective, so we need to evaluate and distinguish others like itraconazole or keto-
conazole, in that cases when Candida strains resist to fluconazole.

Key words: Candidiasis, treatment, miconazole, fluconazole, nystatin.

Introduction Table 1. Predisposing factors.


The incidence of fungal infections has been increasing Systemic Local
over the last decades, being more prevalent in developed Hormonal disorders Epithelial changes
countries (1). An increase incidence of the infections is Physiological disorders Poor oral hygiene
associated with some predisposing factors (Table 1) as Endocrine disorders Loss of vertical dimension
the use of dentures, xerostomia, prolonged therapy with Immunologic disorders Poor fitting dentures
antibiotics, local trauma, malnutrition, endocrine disor- Xerostomia Smoking
ders, increased longevity of people, among other states Drug therapy
that diminish the quality of defense of the individual (2). Alcohol
Oral candidiasis is one of the most common clinical fea-
tures of those patients infected with the human immuno- Oropharyngeal candidiasis is caused by the genus Can-
deficiency virus [HIV], this manifestation was seen in dida; it is possible to isolate about 150 species. Many
up to 90% of individuals infected with HIV (3). of these remain as a commensal micro-organism in hu-

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J Clin Exp Dent. 2014;6(5):e576-82. Treatment of oral candidiasis

mans, which could act as an opportunistic pathogens of- tion; Appropriate use of antifungal drugs, evaluating the
ten associated with predisposing factors attributed to the efficacy / toxicity ratio in each case.
organism, thereby causing acute or chronic infections When choosing between some treatments it will take
(4). The most important of these species is C. albicans, into account the type of Candida, its clinical pathology
which is most commonly isolated from the oral cavity and if it is enough with a topical treatment or requires a
and is believed to be more virulent in humans, occurring more complex systemic type (8), always evaluating the
in approximately 50% of the cases of candidiasis. ratio efficacy and toxicity (9). The different drugs are
Clinically there are a number of different types of oral contained in table 3.
candidiasis (Table 2). Therefore the choice of therapy is Regular oral and dental hygiene with periodic oral exa-
guided by the type of candidiasis. mination will prevent most cases of oral candidiasis, so
The diagnosis of oral candidiasis is essentially clinical it is need to make the patient aware of oral hygiene mea-
and is based on the recognition of the lesions by the pro- sures. Oral hygiene involves cleaning the teeth, buccal
fessional, which can be confirmed by the microscopic cavity, tongue, and dentures. As well as the use of anti-
identification of Candida (5). The techniques available Candida rinses such as Chlorhexidine or Hexetidine, so
for the isolation of Candida in the oral cavity include that they can penetrate those areas where the brush does
direct examination or cytological smear, culture of mi- not. In addition, the need to remove the dentures at night
croorganisms and biopsy which is indicated for cases of and wash it consciously, leaving it submerged in a disin-
hiperplasic candidiasis because this type could present fectant solution like Chlorhexidine (10).
dysplasias (6). This study provides a literature review of the treatment
The treatment of oral candidiasis is based on four fun- of oral candidiasis and its objectives are to establish ge-
daments (7): making an early and accurate diagnosis of neral guidelines for treatment of oral candidiasis; Assess
the infection; Correcting the predisposing factors or un- the drug of choice for local treatment of oral candidiasis;
derlying diseases; Evaluating the type of Candida infec- Assess the systemic treatment for oral candidiasis.

Table 2. Clinical classification.


Acute Chronic Other lesions
Pseudomembranous Pseudomembranous Angular cheilitis
Erythematous Erythematous Denture-associated erythematous
Hyperplastic Median rhomboid glossitis

Table 3. Antifungal agents. Vademecum.


DRUG FORMULATION DOSE ADVERSE EFFECT

Anfotericin b 50mg for infusion 100-200mg/6h Renal, cardiovascular, spinal and neurological

Nystatin Suspension 60ml 4-6ml / 6h Well tolerated.


Ointment 30g 2 to 4 applications / day
Tablets 2 every 8h Uncommon
Nausea, vomiting, gastrointestinal effects

Clotrimazole Gel 1% 3 times / day Occasionally Skin irritation, burning sensation


Tablets 10mg 5 times / day
Miconazole Gel 100mg /6h Uncommon
Burning, irritation, nausea, diarrhea,

Ketoconazole Gel 2% 3 times/ day Nausea, vomiting


Tablets 200mg 1-2/day Abdominal pain.
Suspension 30 or 10cc
Fluconazole Tablets 50 - 100mg/day Nausea, vomiting, diarrhea, abdominal pain.
Suspension 10mg/ml
Itraconazole Capsule 100-200mg/day Nausea, vomiting, diarrhea, abdominal pain.

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Material and Methods As first choice for local treatment has been for years the
A Medline-PubMed search was made using the fo- nystatin at doses of 100 000 IU/ml [5ml 4 times daily]
llowing key words: “ oral candidiasis” OR “oral candi- and amphotericin b at 50mg [5ml 3 times per day]. This
dosis” AND amphotericin, “oral candidiasis” OR “oral choice is because they are poorly absorbed by the in-
candidosis” AND nystatine, “oral candidiasis” OR “oral testinal tract and therefore most of the antifungal is ex-
candidosis” AND miconazole, “oral candidiasis” OR creted without undergoing any change, thereby reducing
“oral candidosis” AND ketoconazole, “oral candidiasis” hepatotoxicity (14). However, the unpleasant taste and
OR “oral candidosis” AND clotrimazole, “oral candidia- prolonged pattern compromise treatment compliance by
sis” OR “oral candidosis” AND fluconazole, “oral can- the patient (14-16).
didiasis” OR “oral candidosis” AND itraconazole, “oral Throughout the years it has been studying the effective-
candidiasis” OR “oral candidosis” AND treatment, “oral ness of other drugs like fluconazole oral solution. Many
candidiasis” OR “oral candidosis” AND “antifungal authors have focused on evaluating the efficacy and
therapy”.The key words were validated by the MeSH safety of fluconazole oral solution for the treatment of
[Medical Subject Headings] dictionary, with use of the oropharyngeal candidiasis, especially pseudomembra-
boolean operator “AND” to relate them. nous type, giving good results, although many studies
The following limits for inclusion of the studies were esta- are still needed (14-18).
blished: articles published from 2000, publications in En- In a recent study conducted in 19 patients with pseudo-
glish and Spanish and publications of studies in humans. membranous candidiasis show that fluconazole suspen-
All systematic reviews, clinical trials, meta-analysis and sion in distilled water [2mg/ml] reaches a 95% cure.
comparative studies were considered in this review. The guideline was to rinse with 5ml of the drug solution
A total of 109 articles were identified, of which 30 were for 1 minute and then spit it out and repeat this action
selected after reading the abstracts. Following analysis 3 times a day for 1 week. Another study which inclu-
of the 30 articles, we finally included a total of 24, since ded 36 children with pseudomembranous candidiasis
those publications that did not fit the aims of the present showed that fluconazole oral suspension 10mg/ml dose
study were excluded. gave better results than nystatin. The main problem was
the poor adherence of the nystatin to the oral mucosa and
Results thus the quick ingestion of the suspension, resulting in a
A total of 24 articles were found about antifungal lower efficiency (14).
treatment, of which 20 were clinical trials, 3 systematic On the other hand, in another study comparing amphote-
reviews and 1 a clinical case (Table 4, 4 (Cont)). ricin b suspension, the fluconazole oral suspension gave
better results in terms of the eradication of Candida (16).
The same was corroborated by Taillandier et al. (18),
Discussion
which reported that fluconazole oral suspension was as
Candida infection today is highly prevalent, especia-
effective as amphotericin b, but it was better accepted
lly the increase in carriers of removable dentures and
by the patient.
poor oral hygiene society. Depending on its virulence,
Fluconazole oral suspension is administered in a dosage
location and type of candidiasis there will carry on one
of 10 mg / ml aqueous suspension by administering 5 ml
treatment or another.
daily for 7 or 14 days. Different studies show that it is
First has been supported the use of conservative mea-
a very effective drug against pseudomembranous candi-
sures before starting drug treatment, promoting good
diasis, as it has good adhesion to the surface of the oral
oral hygiene along with removing the dentures at night,
mucosa and a rapid symptomatic response. It also offers
thereby it will benefit the removal of the biofilm layer
the convenience of a one-daily dosing, which may ex-
generated in the prosthetic surface (11). Dentists should
plain the better patient compliance (14-18).
also correct the predisposing factors and underlying di-
Another topic drug widely used is miconazole (19).
seases and try to promote the use of oral antiseptic and
We found it in the form of gel, applying it directly on
antibacterial rinses such as Chlorhexidine or Hexetidine
the affected area, at doses of 200-500 mg per day, divi-
(12). These measures are very effective in patients with
ded into 4 times. Despite its good properties it has the
denture stomatitis (12). It was also found in the study of
drawback of possible interaction with other drugs, such
Cross et al. (13) that in patients with good oral hygiene
as warfarin. This is because the antifungal inhibit the en-
the recurrence of candidiasis after 3 years was lower.
zyme cytochrome P-450, which affects the clearance of
Regarding the pharmacological treatment of candidiasis
certain drugs (20,21). In addition, this drug is absorbed
can be distinguished between two procedures. Topical
by the intestine, therefore care must be taken when is
drugs, which are applied to the affected area and treat
administrated.
superficial infections and systemic drugs those that are
It has been introduced in the market an alternative pre-
prescribed when the infection is more widespread and
sentation of miconazole. A one-daily miconazole 50 mg
has not been enough with the topical therapy.

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J Clin Exp Dent. 2014;6(5):e576-82. Treatment of oral candidiasis

Table 4. Summarized articles.


Author/ Year Article Type of article Drug Dose Conclusions
/ Sample
Manfredi et In vitro antifungal susceptibility to Clinical trial Itraconazole In vitro Those strains that were
al. (11) 2006 six antifungal agents of 229 Miconazole preparations resistant to fluconazole
Candida isolates from patients n=821 Ketoconazole also were resistant to
with diabetes mellitus Fluconazole other drugs.
Anfotericin b
Koray et al. Fluconazole and/or hexetidine for Clinical trial Hexetidine rinse 2/d Supports the use of
(12) management of oral candidiasis Heksoral® antiseptics or
2005 associated with denture-induced n=61 0,1% hexetidine as a first
stomatitis Fluconazole 50 mg 1/d choice.
Zolax® cap- Conservative i
sules ntervention
Cross et al. Evaluation of the recurrence of Clinical trial Itraconazole 10ml 2/d Best systemic
(13) denture stomatitis and Candida rinse 100mg 2/d- itraconazole
2004 colonization in a small group of n=22 Itraconazole 15d
patients who received itraconazole capsules
Goins et al. Comparison of fluconazole and ny- Clinical trial Nystatin sus- 1ml Fluconazole more
(14) statin oral suspension for treatment n=19 pension 4/d-10d effective
2002 of oral candidiasis in infants Fluconazole
n=15 suspension 10mg/ml
(Diflucan®) 1/d-7d
Epstein et al. Fluconazole mouthrinses for oral Clinical trial Fluconazole 5ml 3/d Clinical improvements
(15) candidiasis in postirradiation oral solution
2002 transplant, and other patients n=19
Lefebvre et A comparative study of the Clinical trial Fluconazole 5 ml (50 mg) Better accepted the
al. (16) efficacy and safety of fluconazole n=123 oral solution 1/d fluconazole
2002 oral suspension and 5ml
amphotericin B oral suspension in n=120l 5ml- 3/d
cancer patients with mucositis Anfotericin b 7-14 d
oral solution
5ml
Sholapurkar Comparison of efficacy of Clinical trial Fluconazole 5ml Mayor cure rate with
et al. (17) fluconazol mouthrinse and n= 27 3/d -14d fluconazole
2009 clotrimazole mouthpaint in the
treatment of oral candidiasis n= 28 Clotrimazole mouthpaint
3/d
Taillander et A comparison of fluconazole oral Clinical trial Fluconazole 5ml(50mg) No significant
al. (18) suspension and amprotericin B oral n=150 oral suspension 1/d difference
2000 suspension in older patients with
oropharyngeal candidosis n= 155 Anfotericin b 5ml- 3/d
oral suspension
Isham et al. Antifungal activity of miconazole Clinical trial Miconazole In vitro pre-
Miconazole presents
(19) 2010 against recent Candida strains n=25 parationgreat inhibitory activity
Pemberton et Miconazole oral gel and drug Clinical case Miconazole gel 125mg/d 3d Decreased the
al. (20) interactions clearance of some
2004 drugs and is absorbed
by the intestine
Miki et al. Warfarin and miconazole oral gel Systematic Miconazole gel 200-400 mg/d Interactions with other
(21) interactions: analysis and therapy review drugs
2011 recommendations based on clinical
data and a pharmacokinetic model
Collins et al. Management of oropharyngeal Systematic Miconazole 50mg 1/d Limited systemic
(22) candidiasis with localized oral review buccal tablets absorption. Good
2011 miconazole therapy: efficacy, efficacy
safety, and patient acceptability
Vazquez et al. Miconazole Mucoadhesive Tablets: Systematic Miconazole 50mg 1/d Little systemic
(23) A Novel Delivery System review mucoadhesive absorption.
2012 n=25 tablets 94.7% efficacy

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Table 4 (Cont). Summarized articles.


Author/ Year Article Type of article Drug Dose Conclusions
/ Sample
Czerninski et A novel sustained-release Clinical trial Clotrimazole 5 times/d Varnish more
al. (24) clotrimazole varnish for local treatment of varnish and prolonged effect
2010 oral candidiasis n= 14 troches
Oji et al. (25) Evaluation and treatment of oral Clinical trial Nystatin rinses 5ml For HIV patients,
2008 candidiasis in HIV/AIDS patient in (micostatin®) 4/d- 14d more effective the
Enugu, Nigeria n=29 Ketoconazole 200mg/ d systemic treatment
tablets 14d (ketoconazole)
(nizoral®)
Bensadoun et Comparison of the efficacy and safety of Clinical trial Miconazole 50mg 1/d Best treatment plan
al. (26) miconazole 50-mg mucoadhesive buccal mucoadhesive the mucoadhesive
2008 tablets with miconazole 500-mg gel in the n=141 tablets tablets
treatment of oropharyngeal Miconazole gel 125mg 4/d
candidiasis
Koks et al. Prognostic factors for the clinical Clinical trial Fluconazole 100mg/d Great efficacy of
(27) effectiveness of fluconazole in the capsules fluconazole
2002 treatment of oral candidiasis in HIV-1- n=28 Diflucan ®
infected individuals
Lyon et al. Correlation between adhesion, Clinical trial Fluconazole In vitro Fluconazole
(28) enzyme production, and preparations reduces erythema
2006 susceptibility to fluconazole in Candida n=99 and cell
albicans obtained from dentures wearers colonization
Oude Lashof An open multicentre Clinical trial Fluconazole 100mg 1/d- Fluconazole better
et al. (29) comparative study of the efficacy, safety capsules 10d result
2004 and tolerance of fluconazole and n=252
itraconazole in the treatment of cancer 200mg 1/d-
patients with oropharyngeal candidiasis Itraconazole 15d
capsules
Kuriyama et In vitro susceptibility of oral Clinical trial Fluconazole In vitro Some Candida
al. (30) Candida to seven antifungal agents Itraconazole preparations species are resistant
2005 n=521 Voriconazole to antifungal drugs
Ketoconazole
Miconazole
Anfotericin b
Nystatin
Brito et al. In vitro antifungal susceptibility of Clinical trial Anfotericin b In vitro pre- Antifungal agents
(31) Candida spp. Oral isolates from HIV- n=71 cepas de Fluconazole parations showed good
2011 positive patients and control individuals Cándida Flucytosine activity against the
Nystatin strains
Ketoconazole
Ally et al. A randomized, double-blind, Comparative Fluconazole 200mg 1/d Voriconazole was at
(32) double-dummy, multicenter trial of clinical trial capsules least as effective as
2001 voriconazole and fluconazole in the Voriconazole 200mg 1/d fluconazole
treatment of esophageal candidiasis in n=256 capsules
immunocompromised patients
Khozeimeh et Comparative evaluation of Clinical trial Ketoconazole 200mg 1/d Miconazole
al. (33) ketoconazole tablet and topical systemic mucoadhesive
2010 ketoconazole 2% in orabase in treatment n=30 Ketoconazole 2% 2/d tablet used as
of Candida-infected denture stomatitis. topical first-line treatment
Miconazole 50 mg because of its good
mucoadhesive tolerance
tablet
Van Roey et Comparative efficacy of topical therapy Clinical trial Miconazole 10mg Miconazole
al. (34) with a slow-release mucoadhesive buccal mucoadhesive mucoadhesive
2004 tablet containing miconazole nitrate n=167 tablet tablets were as
versus systemic therapy with 400 mg effective as other
ketoconazole in HIV-positive patients n=165 Ketoconazole 1/d- 14d systemic drugs
with oropharyngeal candidiasis tablets

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mucoadhesive buccal tablet. It has a limited systemic zole capsules. But when fluconazole failed, itraconazole
absorption. Its performance is mostly local and it has a was prescribed to these patients, having good results. So
convenient application form. Patients are instructed to it is said that it was a good drug for fluconazole-resistant
apply the rounded side of the 50 mg tablet to the upper Candida strains (29).
gum region just above the right or left incisor following As it has been suggested above, it may happen that the
brushing of teeth in the morning. The tablet should be Candida strains were not susceptible to fluconazole, and
held in place until dissolved (22,23). It has the advanta- it has not any effect. In that case it will be used other drugs
ge of being applied once daily instead 5 times a day with like itraconazole or newest ones as voriconazole (30).
clotrimazole (24), and 4 times daily with nystatin (25). Keeping always in mind that strains which were resistant
It has been demonstrated the effectiveness of this new to fluconazole were also resistant to other drugs (31).
form of administration in the study of Bensadoun et al. The new triazol antifungal voriconazole [200 mg per
(26). 141 patients with head and neck cancer with cli- day] has been shown to be a potent drug. Ally et al. (32)
nical signs and symptoms of oropharyngeal candidiasis compared the efficacy of voriconazole and fluconazole
received 50 mg mucoadhesive tablets of miconazole in the treatment of esophageal candidiasis. The success
daily or 125 mg miconazole gel four times per day. Cli- rate was 98.3% for voriconazole and 95.1% for fluco-
nical improvement was not significant between the two nazole. The results show clearly that voriconazole is at
groups, but the mucoadhesive tablets exhibited higher least as effective as fluconazole in the treatment of can-
salivary concentrations and better tolerance for the pa- didiasis. It suggests that this new agent may be a use-
tient. Despite being more expensive, offers an effective, ful alternative for fluconazole-resistant Candida strains
safe, and well tolerated topical treatment for oropharyn- (32). Because of being a new there are little strains resis-
geal candidiasis (22,23,26). tant to voriconazole. The voriconazole has an important
- Systemic treatment: role in the treatment of candidiasis (30), although it is
In spite of knowing the efficacy of the drugs listed abo- still not fully established in the market, so many more
ve, when it comes to a more generalized candidiasis or studies and research would be needed.
immunocompromised patients, these would not be suffi- There have been several studies comparing topical and
cient. For those cases would have to resort to treatment systemic drugs. In a study to treat denture stomatitis have
with systemic drugs (25). been compared the use of ketoconazole tablets [200mg
Since its introduction, fluconazole has been used to treat daily] with topical ketoconazole [2% twice daily] and
systemic Candida infections because of its efficacy and miconazole mucoadhesive tablets (33). Due to the ad-
good tolerability. The appropriate dose is between 50- verse effects of ketoconazole (31) like nausea, vomiting
100 mg daily (27). Furthermore, when dealing with im- and gastrointestinal problems it has been supported the
munocompromised patients, such as those HIV-infected, use of other drugs when treating prosthetic candidiasis
or cancerous, this drug has good effects doubling the (34). Thus the use of miconazole mucoadhesive tablet
dose (28,29). Its efficacy has been demonstrated (27). was established as the drug of first line of defense for
The dose was individualized depending on the severity this type of candidiasis.
and type of candidiasis. Patients with pseudomembra- General treatment guidelines include after the comple-
nous type started with 100 mg fluconazole daily; patients tion of an early diagnosis, the correction of predisposing
with erythematous variety started with 50 mg fluconazo- factors or underlying diseases and maintaining a good
le. Therefore, according to the clinic and the virulence oral hygiene. Moreover using antiseptic agents such as
of the infection the dose would be titrated, giving good Chlorhexidine or Hexetidine, as well as removing den-
results, and increasing the guideline in those cases whe- tures at night. All of that in order to obtain well results in
re the fungal infection did not decrease (27). the treatment of oral candidiasis as first line of defense,
To support the efficacy of this drug it has been compared continuing the application of antifungal drugs. Begin-
with other systemic antifungal agents (29). In one ran- ning with local treatment and keeping up the systemic
domized study, the efficacy of fluconazole [100mg per ones for those patients who do not respond to topical
day for 10 days] and itraconazole [200mg per day for treatment or in immunocompromised patients.
15 days] was compared in patients with oropharyngeal It has recently been found that fluconazole oral suspen-
candidiasis. The results were a clinical and mycologi- sion as a local treatment, at a dose of 2 mg/ml 3 times
cal improvement of 66% for the first group and 54% for daily or 10 mg /ml once daily, gives good clinical results,
those treated with itraconazole. The main conclusion of besides the better patient compliance due to the dosage
this study is that in patients with oropharyngeal candi- and its pleasant taste. Despite not being currently the
diasis, fluconazole has a significantly better clinical and most widely used locally because it requires further cli-
mycological cure rate compared with itraconazole. The nical studies. Nowadays the most used drugs remains in
failures of itraconazole may be explained by drug in- nystatin solution which contain 100 000 IU / ml [5ml 4
teractions and the unpredictable absorption of itracona- times daily] and miconazole gel [200 to 500 mg per day

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J Clin Exp Dent. 2014;6(5):e576-82. Treatment of oral candidiasis

divided into 4 doses]. Moreover miconazole mucoad- 19. Isham N, Ghannoum MA. Antifungal activity of miconazole
hesive tablets [50 mg once daily] which are considered against recent Candida strains. Mycoses. 2010;53:434-7.
20. Pemberton MN, Oliver RJ, Theaker ED. Miconazole oral gel and
effective in the treatment of oropharyngeal candidiasis, drug interactions. Br Dent J. 2004;196:529-31.
but their high cost is one of the main problems. 21. Miki A, Ohtani H, Sawada Y. Warfarin and miconazole oral gel
Fluconazole at doses between 50-100 mg per day is the interactions: analysis and therapy recommendations based on clinical
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50.
tolerability by the patient. However it is important to 22. Collins CD, Cookinham S, Smith J. Management of oropharyngeal
think about the voriconazole which is as effective as flu- candidiasis with localized oral miconazole therapy: efficacy, safety,
conazole but is still under study. Also it is need to know and patient acceptability. Patient Prefer Adherence. 2011;5:369-74.
about other drugs such as itraconazole, which are effec- 23. Vazquez JA, Sobel JD. Miconazole mucoadhesive tablets: a novel
delivery system. Clin Infect Dis. 2012;54:1480-4.
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A novel sustained-release clotrimazole varnish for local treatment of
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